Abstract
BACKGROUND: Depression, a widespread mental disorder, presents significant risks to both physical and mental health due to its high rates of recurrence and suicide. Currently, single-target antidepressants typically alleviate depressive symptoms or delay the progression of depression rather than cure it. Ginsenoside Rg1 is one of the main ginsenosides found in Panax ginseng roots. It improves depressive symptoms through various mechanisms, suggesting its potential as a treatment for depression. MATERIALS AND METHODS: We evaluated preclinical studies to comprehensively discuss the antidepressant mechanism of ginsenoside Rg1 and review its toxicity and medicinal value. Additionally, pharmacological network and molecular docking analyses were performed to further validate the antidepressant effects of ginsenoside Rg1. RESULTS: The antidepressant mechanism of ginsenoside Rg1 may involve various pharmacological mechanisms and pathways, such as inhibiting neuroinflammation and over-activation of microglia, preserving nerve synapse structure, promoting neurogenesis, regulating monoamine neurotransmitter levels, inhibiting hyperfunction of the hypothalamic-pituitary-adrenal axis, and combatting antioxidative stress. Moreover, ginsenoside Rg1 preserves astrocyte gap junction function by regulating connexin43 protein biosynthesis and degradation, contributing to its antidepressant effect. Pharmacological network and molecular docking studies identified five targets (AKT1, STAT3, EGFR, PPARG, and HSP90AA1) as potential molecular regulatory sites of ginsenoside Rg1. CONCLUSIONS: Ginsenoside Rg1 may exert its antidepressant effects via various pharmacological mechanisms. In addition, multicenter clinical case-control and molecular targeted studies are required to confirm both the clinical efficacy of ginsenoside Rg1 and its potential direct targets.